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Disorders of the anterior pituitary gland 

Disorders of the anterior pituitary gland

Chapter:
Disorders of the anterior pituitary gland
Author(s):

Niki Karavitaki

and John A.H. Wass

DOI:
10.1093/med/9780199204854.003.1302_update_001

August 28, 2014: This chapter has been re-evaluated and remains up-to-date. No changes have been necessary.

Update:

Treatment of acromegaly—combined treatment with somatostatin analogues and pegvisomant.

Updated on 30 Nov 2011. The previous version of this content can be found here.
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date: 23 April 2017

The anterior pituitary gland produces growth hormone (GH), luteinizing hormone (LH), follicle-stimulating hormone (FSH), adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone (TSH), and prolactin. Their secretion is regulated by hypothalamic releasing and inhibitory factors delivered via portal capillaries, and by negative feedback inhibition of the cognate hormones produced by target endocrine glands such as the thyroid and adrenal cortex.

Clinical features—presentation of pituitary disease, mostly associated with a space-occupying lesion, may result from (1) local mass effects—often causing headache, visual field defects (most typically bitemporal hemianopia or upper temporal quadrantanopia) and ocular nerve palsies; (2) pituitary hormone deficits—producing wide-ranging effects as a result of single or multiple deficiencies, with GH and gonadotropins (LH and FSH) usually affected first, followed much later by ACTH and TSH; and/or (3) pituitary hormone hypersecretion, usually arising as a consequence of neoplastic proliferation of particular cell types within the gland, producing complex and disabling syndromes such as Cushing’s disease or acromegaly.

Investigation—this includes testing for (1) hormonal hyper- or hyposecretion—measurements of basal levels of pituitary hormones with target gland hormone secretion are usually sufficient for assessment of TSH (thyroxine), FSH/LH (testosterone or oestradiol) and prolactin; dynamic testing is required for the ACTH/cortisol axis and determination of GH deficiency or excess; (2) radiological assessment—MRI is the modality of choice; and (3) neuro-ophthalmological evaluation, including assessment of visual acuity, visual fields and fundoscopy.

Management—the availability of sensitive hormonal assays, replacement hormones and hypothalamic peptides, together with refined neuroimaging methods and neurosurgical techniques, has increased our ability to identify precisely and treat successfully most patients with diseases of the anterior pituitary gland.

Growth hormone

GH deficiency—in children this causes growth failure, and in adults features including decreased energy and quality of life, and increase in fat mass/decrease in muscle mass. The insulin tolerance test is considered the ‘gold standard’ for diagnosis. Goals of GH treatment in adults are to achieve an appropriate clinical response whilst avoiding side effects, and an IGF-1 level in the middle of the reference range.

GH excess—this causes acromegaly, which develops insidiously with multiple clinical features, most notably including local tumour effects, and increase in size of hands, feet, jaw, and skull. Biochemical diagnosis is made by confirming absence of suppression of GH in the oral glucose tolerance test, and by increased serum IGF-1 levels. Management options include (1) surgery—with trans-sphenoidal surgery the treatment of choice for most patients; (2) drugs—including dopamine receptor agonists, somatostatin receptor ligands (e.g. octreotide, lanreotide) and GH receptor antagonists (e.g. pegvisomant); and (3) radiotherapy—generally offered for tumours that have recurred or persisted after surgery in patients with resistance to or intolerance of medical treatment.

FSH and LH

Gonadotropin deficiency—this presents in women with oligo/amenorrhoea, loss of libido, dyspareunia, hot flushes, and infertility; and in men with loss of libido; impaired sexual function; mood impairment; loss of facial, scrotal and trunk hair; decreased muscle bulk and energy. Diagnosis in women is based on clinical features in association with FSH and LH levels that are ‘inappropriately normal’ or low in premenopausal women and low in postmenopausal women; in men there is low morning serum testosterone with low or ‘inappropriately normal’ gonadotropins. Treatment comprises appropriate replacement therapy.

Prolactin

Prolactinomas are the most common pituitary adenomas and typically present with galactorrhoea and hypogonadism, manifesting in men as impotence, infertility, and decreased libido, and in women as oligo/amenorrhoea and infertility. Secondary causes of hyperprolactinaemia must be excluded in any patient with an elevated serum prolactin and serum prolactin levels usually parallel tumour size in those with prolactinomas. Dopaminergic agonists (e.g. cabergoline, bromocriptine, pergolide, quinagolide) are the primary therapy.

ACTH

Chronic ACTH deficiency is associated with fatigue, pallor, anorexia, weight loss, hypotension, hyponatraemia, hypoglycaemia, and eosinophilia. The insulin tolerance test is considered the ‘gold standard’ for diagnosis. Glucocorticoid deficiency can be life threatening and hence replacement with hydrocortisone (or other steroid) in a dose and timing to mimic the normal pattern of cortisol secretion should begin as soon as the diagnosis is confirmed.

Cushing’s disease is caused by chronic exposure to endogenous glucocorticoids (Cushing’s syndrome) produced by the adrenal cortex in response to excess ACTH production by a pituitary corticotroph adenoma. See Chapter 13.7.1 for further discussion.

TSH

Central hypothyroidism is diagnosed when the concentration of thyroxine is decreased and the level of TSH levels is usually normal or low. Clinical presentation is as for primary hypothyroidism (see Chapter 13.4). Treatment is with thyroxine.

Other conditions

Hypopituitarism—can be caused by a range of conditions including pituitary and nonpituitary tumours, hypophysitis, pituitary apoplexy, Sheehan’s syndrome (postpartum), brain injury (traumatic, surgical, irradiation, postinfective), and granulomatous diseases. Clinical manifestations depend mainly on the underlying disease, as well as the type and the degree of the hormonal deficits. Diagnosis and treatment of each pituitary hormone deficit is as described above.

Pituitary adenomas—the most common cause of pituitary disease; may be functioning (resulting in syndromes of hormonal excess) or nonfunctioning (presenting with mass effects). Treatment involves surgery, radiotherapy or medical therapy as described above. Pituitary carcinomas are very rare.

Pituitary apoplexy—occurs primarily in patients with pre-existing pituitary adenomas; results from acute haemorrhage or infarction of the pituitary gland and is characterized by sudden onset of headache, vomiting, visual disturbance, ophthalmoplegia, and altered consciousness. Initial management requires close monitoring of fluid and electrolyte balance and immediate replacement of deficient hormones, especially corticosteroids. Some authorities recommend urgent surgical decompression in some cases.

Craniopharyngiomas—these epithelial tumours can present with pressure effects and/or compomised hypothalamo-pituitary function. First-line treatment usually comprises surgery with or without adjuvant external beam irradiation.

Hypophysitis—may be primary (granulomatous, xanthomatous or lymphocytic) or caused by a known agent or systemic disease. Differential diagnosis is from pituitary adenoma. Treatment is controversial and includes replacement of defective endocrine function and/or reducing the size of the pituitary mass.

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